Fever-range whole body thermotherapy combined with oxaliplatin: A curative regimen in a pre-clinical breast cancer model
| Autor: | F. R. Strebel, Diana Chan, R. Wanda Rowe, Zahid H. Siddik, Joan M C Bull, Wanleng Deng, Jesse M. Proett, Guangan He |
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| Rok vydání: | 2010 |
| Předmět: |
Hyperthermia
Oncology Cancer Research medicine.medical_specialty Fever Organoplatinum Compounds Physiology medicine.medical_treatment Antineoplastic Agents Breast Neoplasms Adenocarcinoma Gastroenterology Drug Administration Schedule Article DNA Adducts In vivo Low-dose chemotherapy Cell Line Tumor Physiology (medical) Internal medicine medicine Animals Platinum Chemotherapy Dose-Response Relationship Drug business.industry Hyperthermia Induced medicine.disease Combined Modality Therapy Rats Inbred F344 Rats Oxaliplatin Disease Models Animal Regimen Treatment Outcome Toxicity Female business medicine.drug |
| Zdroj: | International Journal of Hyperthermia. 26:565-576 |
| ISSN: | 1464-5157 0265-6736 |
| Popis: | Studies were conducted to test whether fever-range whole body thermal therapy would boost the efficacy of oxaliplatin chemotherapy without substantial toxicity.The effect of mild heat (40 degrees C) on oxaliplatin cytotoxicity, cellular uptake, and platinum-DNA adduct formation was studied in vitro using the MTLn3 tumour cell line. In vivo oxaliplatin was administered at various doses and times before, during and after fever-range thermal therapy (6 h at 40 degrees C) to rats bearing an MTLn3 mammary adenocarcinoma. Tumour growth, survival, and toxicity were measured to determine treatment outcome.Heating halved the oxaliplatin IC-50 dose for MTLn3 cells. Cellular uptake of platinum and platinum adducts increased by 34% and 36%, respectively, with heat. In vivo, 50% of all rats given 10 mg/kg oxaliplatin 24 h before thermal therapy were completely immunologically cured, while a further 11% regressed their primary tumour but ultimately succumbed to metastases, and 17% experienced a limited response with increased survival. The curative response occurred only in a narrow range of doses, with most cures at 10 mg/kg. Thermochemotherapy-treated, but uncured, animals had delayed incidence and slowed growth of metastases. Anti-tumour efficacy was greatest, and toxicity was least, when oxaliplatin was administered 12 or 24 h before fever-range whole body thermal therapy.When properly dosed and scheduled, oxaliplatin thermochemotherapy achieved permanent eradication of all primary and metastatic tumours in 50% of animals, seemingly through an immune response. Successful clinical translation of this protocol would yield hitherto unseen cures and substantial improvement in quality of life. |
| Databáze: | OpenAIRE |
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